tbuckley/cabot-search huggingface dataset:
Primary mediastinal seminoma: Treatment and survival outcomes.
Authors: Rebecca Hassoun, Sandra K. Althouse, Jennifer King, Nasser H. Hanna, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2023)

422 Background: Primary mediastinal pure seminoma is a rare entity and there is no clear consensus for optimal management. We report treatment and survival outcomes of patients with primary mediastinal seminoma evaluated at our institution. Methods: The Indiana University (IU) testicular cancer database was queried for patients with primary mediastinal seminoma. 21 patients evaluated at IU between 1994-2022 were included in this analysis. Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) analysis. Results: Median age at diagnosis was 40.7 (range, 19.4-54.2). 18 (85.7%) patients were IGCCCG good risk and 3 (14.3%) were intermediate risk. Median pre-chemotherapy hCG was 10.3 (range, 0.6-1500). 12 (57.1%) patients had metastatic disease. Metastatic sites included mediastinal/supraclavicular lymph nodes in 9 patients (42.9%), lungs in 3 (14.3%), retroperitoneal lymph nodes in 3 (14.3%), brain in 1 (4.8%), liver in 1 (4.8%), adrenal gland in 1 (4.8%), kidney in 1 (4.8%) and bone in 1 (4.8%). First-line chemotherapy was BEPx3 in 9 (42.9%) patients, EPx4 in 4 (19.0%), BEPx4 in 3 (14.3%), BEPx3 + EPx1 in 2 (9.5%), VIPx4 in 2 (9.5%), and VIPx1 + BEPx3 in 1 (4.8%). With a median follow-up of 4.65 years from first-line chemotherapy start date, 3 (14.3%) patients progressed after first-line chemotherapy. Among patients who progressed, salvage 2 nd line therapy was high-dose chemotherapy in 1 patient. 1 patient received more than 2 lines of therapy. 1 patient underwent surgical resection of residual mediastinal mass due to concern for local progression, with pathology revealing necrosis only. The 5-year progression-free survival (PFS) from first-line chemotherapy was 82.4% (95% CI 54.7-93.9). The 5-year overall survival (OS) was 94.1% (95% CI 65.0-99.1). At last follow-up, 20 (95.2%) patients had no evidence of disease, and 1 (4.8%) was dead of disease. Conclusions: Patients with primary mediastinal pure seminoma have high cure rates with risk adapted cisplatin-based combination chemotherapy. Despite residual masses, further surgical resection or radiation is not required in the vast majority of these patients and these residual masses can be safely monitored with surveillance.
Real-world homologous recombination repair (HRR) mutation testing patterns in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in the United States (US).
Authors: Pedro C. Barata, Rachel Montgomery, Matthew Last, Liane Gillespie-Akar, Jonathan Nazari, Alexander Niyazov
Journal: Journal of Clinical Oncology (2023)

99 Background: A subset of pts with metastatic prostate cancer have HRR mutations. These can be either germline or somatic mutations. Previous studies have established a prognostic and predictive role of HRR mutations and there are ongoing trials (e.g., TALAPRO-3, AMPLITUDE) exploring combination strategies of poly-ADP ribose polymerase inhibitors (PARPi) with novel hormonal therapies (NHT). Therefore, it is relevant to establish baseline HRR testing rates in the real-world setting. This study assessed real-world (rw) HRR testing patterns in pts with mCSPC in the US and described characteristics of tested vs untested pts. Methods: Data were drawn from the Adelphi Prostate Cancer Disease Specific Programme; a point-in-time questionnaire administered to oncologists and urologists in the US between January-August 2020. Physicians abstracted medical records for the next 4-9 pts receiving active drug treatment for mCSPC. Study variables included pt demographics, clinical factors, physician characteristics, and testing status for at least 1 of 12 HRR genes of interest ( ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C). Pt demographics and clinical characteristics were compared between groups using t-tests for continuous and chi-squared or Fisher’s exact test for categorical variables. A multiple logistic regression model was used to assess factors associated with odds of HRR testing. Results: A total of 71 physicians reported on 204 pts with mCSPC. The median age was 68.8. 57/204 (28%) pts were tested for HRR mutations using germline or tumor testing. Pts who were not HRR tested were older compared to HRR tested pts (69.6 vs 66.8, P = 0.038). More pts currently receiving care by an oncologist had a HRR mutation test vs. pts currently receiving care by a urologist [50/156 (32%) vs 7/48 (15%), P =0.02]. According to the multiple logistic regression model, having a known family history of prostate cancer [OR = 3.9 (95% CI: 1.1 – 13.6); P = 0.04], and having visceral metastases at mCSPC diagnosis [OR=4.9 (95% CI: 2.0 – 12.1); P = 0.001] were associated with a significantly higher odds of receiving a HRR mutation test. Conclusions: In this rw US study of adult patients with mCSPC, most patients did not receive HRR testing. Disparities in HRR mutation testing were observed, suggesting that clinical characteristics may influence decisions to test for HRR mutations. Focused efforts to increase HRR mutation testing should be implemented.
Association of biomarkers and response to immune checkpoint inhibitors (ICIs) in patients with metastatic urothelial carcinoma (mUC) with high and low tumor mutation burden (TMB).
Authors: Tanya Jindal, Xiaolin Zhu, Li Zhang, Kevin R Reyes, Prianka Deshmukh, Ivan de Kouchkovsky, Vipul Kumar, Edward Maldonado, Chase Shipp, Daniel H Kwon, Hala Borno, Rohit Bose, Arpita Desai, Rahul Raj Aggarwal, Sima P. Porten, Eric Jay Small, Lawrence Fong, Jonathan Chou, Terence W. Friedlander, Vadim S Koshkin
Journal: Journal of Clinical Oncology (2023)

534 Background: ICIs are frequently used as therapy in mUC, but only a minority of patients (pts) respond to treatment. High TMB is associated with improved outcomes to ICIs. However, much is unknown about biomarkers associated with ICI outcomes in pts with high and low TMB respectively. Methods: We retrospectively identified mUC pts with known TMB status and available next generation sequencing (NGS) results treated with ICI monotherapy at our institution. TMB high was defined as ≥ 10 mutations/Mb, with the rest being TMB low. Somatic alterations present in ≥10% pts ( ARID1A, CCND1, CDKN2A, CDKN2B, ERBB2, FGF3, FGF4, FGF19, FGFR3, KDM6A, MDM2, MLL2, PIK3CA, RB1, TERTp, TP53, TSC1), and presence of DNA damage response (DDR) alterations were assessed as biomarkers of interest. Within the TMB-high and TMB-low pt groups we separately assessed patients based on the presence or absence of these somatic alterations, APOBEC mutational signature and high PD-L1 expression. Log rank test was used to determine differences in overall survival (OS) and progression free survival (PFS) among these groups. P-value ≤0.05 was considered significant. Results: Among 107 mUC pts treated with ICI monotherapy between 12/2014 and 3/2022 who had NGS data (UCSF500, FoundationOne, Strata), 85 pts had TMB data, including 47 TMB high pts and 38 TMB low pts. Among 85 pts with known TMB status, median age was 76 yrs, the majority were male (55, 65%), Caucasian (57, 67%), had pure urothelial histology (46, 55%) and were treated with ICIs in frontline setting (47, 55%). Median OS was 17.2 mos and median PFS was 3.42 mos. In TMB high pts, presence of DDR , MLL2, KDM6A, PIK3CA and TERTp alterations were each associated with improved outcomes, while presence of CDKN2B alterations was associated with inferior outcomes (Table). Among TMB low pts, those with RB1 alterations had shorter mOS (11.3 months vs 17.2 months; p=0.04) compared to wild-type pts. Conclusions: In this single-center retrospective analysis of mUC pts, we identified somatic alterations that were predictive of outcomes with ICI treatment in TMB high and TMB low pts respectively. Further exploration of biomarkers in patients stratified by TMB status is warranted in larger cohorts. [Table: see text]
Prognostic utility of linear segmentation in nonmetastatic renal cell carcinoma: Correlation of overall survival with muscle mass.
Authors: Benjamin Schmeusser, Eric Midenberg, Arnold Raul Palacios, Nikhil Vettikattu, Dattatraya H Patil, Reza Nabavizadeh, Alexandra Medline, Michelle Higgins, Sarah P. Psutka, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2023)

617 Background: In renal cell carcinoma (RCC) and other solid organ malignancies, sarcopenia has been associated with decreased survival and increased perioperative complications. Traditional body composition analysis is an expensive and time extensive process. As a modifiable risk factor, more clinic friendly methods to identify patients with low muscle composition is of interest. Linear segmentation on routine imaging has been proposed as a fast, reliable and reproducible alternative. This study assesses the prognostic ability of linear segmentation in patients with nonmetastatic RCC. Methods: Patients that underwent nephrectomy for nonmetastatic RCC from 2005-2021 at an academic referral center were identified. Linear segmentation of the bilateral psoas/paraspinal muscles was completed on preoperative imaging obtained within 60 days of surgery. Cox proportional-hazards analysis was used to determine association between total muscle index and overall survival. Results: 532 (388 clear cell) patients were analyzed and a median total muscle index was 28.6 (25.8-32.5) for women and 33.3 (29.1-36.9) for men. As a binary variable, lower total muscle index was significantly associated with decreased survival in both the full (HR=1.96, 95% CI 1.32-2.90, p&lt;0.001) and clear cell only cohorts (HR=1.78, 95% CI 1.08-2.75, p=0.022). As a continuous variable, unit increases in total muscle index were significantly associated with improved survival in the full cohort (HR=0.95, 95% CI 0.92-0.99, p=0.006) and the clear cell only cohort (HR=0.95, 95% CI 0.92-0.99, p=0.016). Conclusions: Assessment of muscle composition via linear segmentation on routinely obtained preoperative imaging is a clinically feasible technique with prognostic utility in patients with localized RCC. In this cohort of patients with nonmetastatic RCC, linear segmentation demonstrated significant associations with overall survival as a binary and continuous variable. This simplified technique may allow for routine inclusion of body composition into clinical decision making. [Table: see text]
Cost savings associated with palliative care among patients with genitourinary malignancies.
Authors: Phichai Chansriwong, Nintita Sripaibookij Thokanit, Siriporn Semsarn, Pinyo Utthiya, Vijj Kasemsup
Journal: Journal of Clinical Oncology (2023)

474 Background: The cost of cancer treatment has increased significantly in recent decades, and highest costs incurred in the last 6-months of life. Patients’ health insurance status is a factor influencing to cost of care in different from individuals’ ability to access hospital care. 80% of Thai people use the Thailand’s Universal Coverage Scheme (UCS), about 15% use the Civil Servants Medical Benefit Scheme (CSMBS). Only CSMBS can reimburse all costs of in-patient care, but UCS had to co-pay at some cost. All health scheme is equality accessibility to palliative care. Early integrated palliative care services improve the GU malignancy patients care experience, decreases healthcare utilization, and improved quality of life. Study aim was to examine Hospital-based palliative care interventions in GU malignancy patients may reduce costs. Methods: A retrospective claims database in Ramathibodi Hospital was analyzed, that included cancer patients had a medical claim for death between Jan 1, 2016 - Dec 31, 2020. Our study compared cost in patients receiving palliative care (PC) and patients receiving usual care. Costs were determined by summing paid amounts on all hospital services used within the last 6, 3 and 1 months before death, including cancer-related inpatient service, emergency room visits, cancer-related outpatient services and other hospital services with cancer diagnosis. Results: Of the 1,772 cancer patients who died, 289 (16.3%) integrated treated with PC matched to 1,483 (83.7%) were usual care patients. 107 Genitourinary Malignancies patients including 44 TCC, 36 Prostate, 22 RCC and 2 Testicular cancer, that 22 (20.6%) integrated treated with PC. Median age was 72.4 years. Patients categorized as CSMBS 48% and UCS 44.4%. The PC group had $10,244.1 (+/- 8,705.6) in last 3 months hospital costs that significantly less than in usual care $(17,174.3 +/-14,262.5) (P= 0.032) that PC group had significant reductions in medications, laboratory, and intensive care unit costs compared with usual care patients. Direct costs of inpatient care in the last 3 months of life for patients were lower in patient who received earlier PC that patients who received PC consults &lt; 90 days was $9,728.8 (+/- 1,044.5) and patients received PC consults &lt; 30 days cost was $12,517.7 +/- 1,476. Patients in SSS and UCS had a significantly saving cost when they received PC consultation, P=0.032. However, there was no difference in CSMBS. Conclusions: Integrated palliative care in caring GU malignant patients associates with significant hospital cost savings. Insurance status not limited in access to palliative care consultation, but influences in cost of end-of-life care.
Characterization of clinical outcomes among patients with advanced chromophobe renal cell carcinoma (ChRCC) treated with first-line immunotherapy (IO)-based regimens.
Authors: Chris Labaki, Ziad Bakouny, J Connor Wells, Kosuke Takemura, Renee Maria Saliby, Luis A Meza, Georges Gebrael, Camillo Porta, Jae-Lyun Lee, Naveen S. Basappa, Guillermo De Velasco, Rana R. McKay, Sumanta Monty Pal, Neeraj Agarwal, Frede Donskov, David A. Braun, Elizabeth Henske, Wanling Xie, Daniel Yick Chin Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2023)

654 Background: IO-based regimens have demonstrated substantial efficacy in the management of metastatic clear-cell RCC (mccRCC), where they currently represent the standard of care. ChRCC has a dismal prognosis in the metastatic setting. Recent clinical trials evaluating IO-based regimens across non-ccRCC subtypes identified a preliminary poor response in advanced ChRCC, but were limited by low sample sizes. We sought to comprehensively evaluate the outcomes of patients with ChRCC treated with IO-based regimens. Methods: Using real-world data from the International Metastatic RCC Database Consortium (IMDC), we conducted a retrospective analysis of patients with advanced ChRCC who received IO-based therapies, including dual IO therapy or IO + VEGF targeted therapy (VEGF-TT), in the first-line setting. The primary outcome was overall survival (OS). Secondary outcomes included time to treatment failure (TTF) and ORR. Cox proportional hazards models were used to adjust for age and IMDC risk groups as covariates. A logistic regression was used to determine the association between the odds of achieving a response and RCC subtype. Results: We identified 31 patients with advanced ChRCC and 856 patients with ccRCC treated with IO-based therapies in the first-line setting, with a median age of 61.5 years (IQR: 51.5-69.0). Compared to patients with ccRCC who received IO-based therapies as initial regimens, patients with ChRCC had a lower OS (median OS: 24.7 vs. 50.5 months, respectively; p&lt;0.001) and a lower TTF (median TTF: 4.5 vs. 11.0 months, respectively; p&lt;0.001). Among patients with an evaluable objective response, the ORR was lower among patients with advanced ChRCC, as opposed to those with ccRCC (ORR: 12.0 vs 47.1%, respectively; p&lt;0.001). When evaluating first-line treatment with VEGF-TT monotherapy (sunitinib or pazopanib), no difference in outcomes was found between patients with ChRCC (n=122) and ccRCC (n=6,379) in relation to the primary endpoint of OS, while TTF and ORR suggested better outcomes for ccRCC (Table). Conclusions: In this real-world study, patients with metastatic ChRCC appear to display poor clinical outcomes even with IO-based regimens, as compared to ccRCC. The molecular determinants of poor response require further investigations. [Table: see text]
Patterns of failure after radiotherapy (RT) in patients with prostate cancer re-staged with <sup>18</sup>F-DCFPyL PSMA-PET: A regional cohort analysis.
Authors: Aruz Mesci, Sneha Mukherjee, Mohammad Gouran-Savadkoohi, Anil Kapoor, Glenn Bauman, Himu Lukka, Ian S. Dayes, Kara Schnarr, Mira Goldberg, Kimmen Quan, Katherine A. Zukotynski, Theodoros Tsakiridis
Journal: Journal of Clinical Oncology (2023)

45 Background: In Ontario, PSMA-PET is available to patients with prostate cancer who experience biochemical failure after definitive primary RT (pRT) or salvage/adjuvant RT (sRT) through a provincial registry study (PREP protocol). Here we review patterns of PSMA-PET-detected failure after primary (pRT) or salvage/adjuvant RT (sRT) radiotherapy (RT) in cohorts of PREP-registry patients from the Local Health Integration Network (LHIN) 4 region. Methods: With ethics approval, we retrospectively analyzed patients imaged with PSMA-PET in Hamilton, Ontario, Canada, after biochemical failure, following pRT or sRT. Demographic, clinical and treatment parameters as well as PSMA-PET results were collected. Results: Between April 2019 and December 2021, 104 pRT and 91 sRT patients were imaged with 18 F-DCFPyL PSMA-PET. Median PSA (ng/mL) before PSMA-PET for the two groups was 5.0 (IQR:3.1-8.9) and 1.3 (IQR:0.6-3.4). The percentages of Prostate or Prostatic bed RT alone (Pr-RT) and Pr + pelvic Lymph Node RT (Pr+LN-RT) RT treatments, were Pr-RT:76% vs Pr+LN-RT:24% for the pRT group and Pr-RT:49.4% vs Pr+LN-RT:50.6% for the sRT group, respectively. Rates of PSMA-PET detected local, pelvic lymph node and distant recurrence are shown. In the pRT group, increasing D’Amico risk category (low to high risk) was associated with lower risk for local and increased risk for pelvic and distant metastasis. Pelvic RT was associated with reduce risk for local recurrence in the pRT but not in the sRT group. Conclusions: In this cohort of patients PSMA-PET detected a considerable risk for local recurrence in patient treated with pRT. A high number of patients are detected with pelvic-only disease recurrence, but pelvic RT seems to be associated with reduction in this risk only in the pRT population. Studies with PSMA-PET at baseline, before pRT or sRT, may help discern better patients that would benefit from pelvic RT and systemic therapy.[Table: see text]
Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer.
Authors: Ahmed Mahmoud, Igor Frank, Mohamed E. Ahmed, Jacob Orme, Roxane Lavoie, Prabin Thapa, Brian Addis Costello, John Cheville, Sounak Gupta, Haidong Dong, Fabrice Lucien
Journal: Journal of Clinical Oncology (2023)

548 Background: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. Methods: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher’s exact test and postoperative survival using Kaplan–Meier survival curves and Cox regression model. Results: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06–5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18–6.04, p = 0.019). Conclusions: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.
Planned interim analysis of perioperative safety of fluzoparib combined with abiraterone in the neoadjuvant treatment of locoregional high-risk prostate cancer: Results from multicenter, phase 2 FAST-PC trial.
Authors: Yao Zhu, Tingwei Zhang, Beihe Wang, Huajun Li, Dingwei Ye
Journal: Journal of Clinical Oncology (2023)

356 Background: Previous studies confirmed that the combination of PARP inhibitors and abiraterone might bring survival benefits to prostate cancer (PC) patients (pts) regardless of HRR mutation status. Hence, we conducted a single-arm, multicenter, phase II trial (FAST-PC, NCT05223582) to investigate safety and efficacy of fluzoparib combined with abiraterone and androgen deprivation therapy (ADT) in the neoadjuvant treatment of locoregional high-risk PC. Herein, a planned interim analysis of safety outcome of this study was reported. Methods: FAST-PC trial enrolled pts with only pelvic lymph node metastasis or high-risk localized (cT3-4 or prostate specific antigen (PSA) &gt;20 ng/mL or Grade Group ≥4) PC. Eligible pts received fluzoparib (150mg PO BID), abiraterone (1000mg PO QD), prednisone (5mg PO BID), and ADT for 24 weeks followed by minimally invasive radical prostatectomy (RP). Perioperative outcomes were collected and evaluated during treatment period and follow-up period which was three months after surgery. Post-surgery AEs within 90 days were classified by Clavien-Dindo. Results: As of Sep 2022, 31 pts were recruited. All the 12 pts (patient No.1 to No.12) who have completed both the 24-week neoadjuvant regimen and surgery were analyzed. Baseline characteristics were shown in table. None of them were lost to follow-up or discontinued the protocol due to adverse events (AEs). The common AEs related to medication including anemia (4, 33.3%), hypokalemia (3, 25.0%), and liver dysfunction (3, 25.0%). As for post-surgery outcomes, median days of hospitalization, surgical time, and blood loss were 8.5 days (6-12.8), 144 minutes (16.5-171.3), and 100ml (50-200), respectively. Overall, 7 (58.3%) pts experienced post-surgery AEs of any grade, in which 4 (33.3%) were grade 1 and 3 (25.0%) were grade 2. 6 (50.0%) experienced fever, and 2 (16.7%) had urinary tract infections. Of note, pulmonary thrombosis (grade 2) was diagnosed in one patient after RP. Conclusions: Our data represent the first prospective evidence supporting the perioperative safety in locoregional high-risk PC pts who received neoadjuvant fluzoparib combined with abiraterone and ADT. The combined regimen is generally safe and reliable, while special vigilance should be paid to the occurrence of anemia, hypokalemia and liver dysfunction. Clinical trial information: NCT05223582 . [Table: see text]